Dose Confirmation Trial of AAV5-hFIXco-Padua

NCT03489291 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CSL222_2001 (CT-AMT-061-01)
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 4

Brief Summary

This is an open-label, single-dose, single-arm, multi-center trial, with a screening, a treatment + post-treatment follow-up phase, and a long-term follow-up phase. The IMP AMT-061 is a recombinant adeno-associated viral vector of serotype 5 (AAV5) containing the Padua variant of a codon-optimized human FIX complementary deoxyribonucleic acid (cDNA) under the control of a liver-specific promoter. The IMP is identified as AAV5-hFIXco-Padua (AMT- 061). The pharmaceutical form of AMT-061 is a solution for intravenous infusion. The administered dose of AMT-061 will be 2 x 10\^13 gc/kg.

Conditions

Hemophilia B

Keywords

Hemophilia,; Gene Therapy; Bleeding; Factor IX; FIX; viral vector; Padua

Outcome Measures

Primary Outcomes (1)

• Factor IX Activity Levels

  To confirm that a single dose of 2x10\^13 gc/kg AMT-061 (CSL222) resulted in factor IX activity levels of ≥5% at 6 weeks after dosing measured by the one-stage (activated partial thromboplastin \[aPTT\]-based) assay.

  6 weeks post-dose

Secondary Outcomes (15)

• Annualized Exogenous Factor IX Usage

  52 weeks post-dose

• Annualized Bleeding Rate (ABR)

  5 years post-dose

• Factor IX Activity Levels

  52 weeks post-dose

• Number of Participants Remaining Free of Continuous Prophylaxis

  1 year post-dose

• Annualized Exogenous Factor IX Usage Post-Continuous Prophylaxis

  Up to 5 years post-dose

Study Arms (1)

Single infusion of AMT-061

EXPERIMENTAL

Subjects will receive a single infusion of AAV5-hFIXco-Padua (AMT- 061) at baseline. After IMP administration (post IMP), subjects will be monitored for tolerance to the IMP and detection of potential immediate AEs at the clinical trial site for 24 hours (overnight stay).

Genetic: AAV5-hFIXco-Padua (AMT-061)

Interventions

AAV5-hFIXco-Padua (AMT-061) GENETIC

Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061)

Single infusion of AMT-061

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Hemophilia B is an X-linked, recessive condition, since it occurs almost exclusively in males. Females typically are asymptomatic carriers. Therefore eligibility is restricted to male participants.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male
• Age ≥18 years
• Subjects with congenital hemophilia B classified as severe or moderately severe
• \>20 previous exposure days of treatment with FIX protein

You may not qualify if:

• History of FIX inhibitors
• Positive FIX inhibitor test at screening
• Select screening laboratory values \> 2 times upper normal limit:
• Positive human immunodeficiency virus (HIV) at screening, not controlled with anti-viral therapy
• Active infection with Hepatitis B or C virus at screening
• History of Hepatitis B or C exposure, currently controlled by antiviral therapy

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (4)

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

University of California, Davis

Sacramento, California, 95817, United States

Location

University of California, San Diego

San Diego, California, 92122, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (4)

• von Drygalski A, Gomez E, Giermasz A, Castaman G, Key NS, Lattimore SU, Leebeek FWG, Miesbach WA, Recht M, Monahan PE, Le Quellec S, Pipe SW. Completion of phase 2b trial of etranacogene dezaparvovec gene therapy in patients with hemophilia B over 5 years. Blood Adv. 2025 Jul 22;9(14):3543-3552. doi: 10.1182/bloodadvances.2024015291.

  PMID: 40188458 DERIVED

• O'Connell N, van der Valk P, Le Quellec S, Gomez E, Monahan PE, Crary SE, Coppens M, Lemons R, Castaman G, Klamroth R, Symington E, Quon DV, Kampmann P. Invasive procedures and surgery following etranacogene dezaparvovec gene therapy in people with hemophilia B. J Thromb Haemost. 2025 Jan;23(1):73-84. doi: 10.1016/j.jtha.2024.08.027. Epub 2024 Sep 26.

  PMID: 39341368 DERIVED

• von Drygalski A, Gomez E, Giermasz A, Castaman G, Key NS, Lattimore SU, Leebeek FWG, Miesbach WA, Recht M, Gut R, Dolmetsch R, Monahan PE, Le Quellec S, Pipe SW. Stable and durable factor IX levels in patients with hemophilia B over 3 years after etranacogene dezaparvovec gene therapy. Blood Adv. 2023 Oct 10;7(19):5671-5679. doi: 10.1182/bloodadvances.2022008886.

  PMID: 36490302 DERIVED

• Von Drygalski A, Giermasz A, Castaman G, Key NS, Lattimore S, Leebeek FWG, Miesbach W, Recht M, Long A, Gut R, Sawyer EK, Pipe SW. Etranacogene dezaparvovec (AMT-061 phase 2b): normal/near normal FIX activity and bleed cessation in hemophilia B. Blood Adv. 2019 Nov 12;3(21):3241-3247. doi: 10.1182/bloodadvances.2019000811.

  PMID: 31698454 DERIVED

MeSH Terms

Conditions

Hemophilia B; Hemophilia A; Hemorrhage

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: CSL Behring

clinicaltrials@cslbehring.com

+1 610-878-4000

Study Officials

• Steven Pipe, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: open-label, single-dose, single-arm, multi-center trial

Study Record Dates

• First Submitted: March 19, 2018
• First Posted: April 5, 2018
• Study Start: July 24, 2018
• Primary Completion: October 30, 2018
• Study Completion: September 21, 2023
• Last Updated: June 28, 2024
• Results First Posted: June 16, 2022

Record last verified: 2024-06

Locations

US (4)